两样本孟德尔随机化分析肠道菌群与肺癌的因果关系

Association of lung cancer and gut microbiota:A two-sample Mendelian randomization analysis

目的探索肺癌与肠道菌群之间潜在的因果关系。方法孟德尔随机化(M e n d e l i a n randomization,MR)研究使用了肠道菌群和肺癌的全基因组关联研究(genome-wide association studies,GWAS)。肠道菌群作为暴露因素,工具变量从18340名参与者的GWAS中确定。来自欧洲的肺癌GWAS研究作为结局变量,包括29266例肺癌患者,56450例对照。逆方差加权分析方法(inverse-variance weighted,IVW)作为主要分析方法。敏感性分析用于检验MR分析结果是否可靠。结果在IVW方法中,副拟杆菌属[OR=1.258,95%CI(1.034,1.531),P=0.022]和拟杆菌门[OR=1.192,95%CI(1.001,1.419),P=0.048]与肺癌呈正相关,双歧杆菌科[OR=0.845,95%CI(0.721,0.989),P=0.037]和双歧杆菌目[OR=0.865,95%CI(0.721,0.989),P=0.037]与肺癌之间成负相关。敏感度分析显示没有反向因果关系、多效性和异质性的证据。结论副拟杆菌属和拟杆菌门与肺癌风险增加有关,而双歧杆菌科和双歧杆菌目减少肺癌发生风险。我们的研究支持几个肠道菌群和肺癌之间的潜在因果关系。需要进一步研究来探究肠道菌群如何影响肺癌的发展。

Objective To assess any potential associations between lung cancer and gut microbiota.Methods Mendelian randomization(MR)analysis was carried out by utilizing summary data from genome-wide association studies(GWAS)of the gut microbiota and lung cancer.The gut microbiota served as an exposure.Instrumental ariables(IVs)were identified from the GWAS of 18340 participants.The GWAS study of lung cancer from Europe served as an outcome,including 29266 lung cancer patients and 56450 controls.We used the inverse-variance weighted(IVW)method as the primary analysis.Sensitivity analysis was used to test the reliability of MR analysis results.Results IVW results showed that Genus Parabacteroides(OR=1.258,95%CI 1.034 to 1.531,P=0.022)and Phylum Bacteroidetes(OR=1.192,95%CI 1.001 to 1.419,P=0.048)had a positive causal association with lung cancer,and there was a negative causal association between family Bifidobacteriaceae(OR=0.845,95%CI 0.721 to 0.989,P=0.037)and order Bifidobacteriales(OR=0.865,95%CI 0.721 to 0.989,P=0.037)with lung cancer.Sensitivity analysis showed no evidence of reverse causality,pleiotropy,and heterogeneity.Conclusion This study demonstrates that Genus Parabacteroides and Phylum Bacteroidetes are related to an increased risk of lung cancer,family Bifidobacteriaceae and order Bifidobacteriales can reduce the risk of lung cancer.Our thorough investigations provide evidence in favor of a potential causal relationship between a number of gut microbiota-taxa and lung cancer.To demonstrate how gut microbiota influences the development of lung cancer,further research is necessary.